Antitumor Activity of Ligustilide Against Ehrlich Solid Carcinoma in Rats via Inhibition of Proliferation and Activation of Autophagy

Alshehri, Afnan F; Khodier, Ahmed E; Al-Gayyar, Mohammed M

doi:10.7759/cureus.40499

Cited by 6 publications

(6 citation statements)

References 38 publications

(45 reference statements)

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“…Notably, LIG promoted apoptosis in ESC by significantly increasing the expression of Bcl2. 29 It also dramatically inhibits the viability and migration of HCC and oral cancer cells. 31 In this paper, we investigated the functions of LIG and NBP in U251 the proliferation, migration, invasion, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway

Li,

Zhang,

Liu

et al. 2023

OTT

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Background: Ligustilide (LIG) and n-butylphthalide (NBP) have neuroprotective effects in cerebral ischemia; however, their roles in gliomas are not well-known.This study aimed to explore the anti-glioma effects of LIG and NBP individually and the synergistic effects of temozolomide (TMZ) via the PI3K/Akt Signaling Pathway. Materials and Methods: Cytotoxicity of LIG and NBP alone and in combination with TMZ in U251 cells was determined using the CCk-8. The effect of compounds alone or in combination on cell migration was detected using the wound healing assay, and the invasion was evaluated by transwell assays, respectively. Cell apoptosis was quantified by flow cytometry and the changed expressions of proteins were detected by Western blotting. Results:The results showed that LIG and NBP significantly inhibited the growth of U251 cells at concentrations of 4-10 µg/mL and 1.5-6 µg/mL in a dose-dependent manner (p<0.05, p<0.01). The combination of 20 µg/mL TMZ with LIG in the concentration range of 4-10 µg/mL or with NBP of 0.5-6 µg/mlachieved synergistic effect towardsU251 cells. LIG and NBP, alone or in combination with TMZ, markedly inhibited cell invasion (p< 0.001) and enhanced apoptosis (p< 0.05). The combination of TMZ with LIG or NBP markedly inhibited cell migration (p< 0.001). Western blot analysis showed that LIG, NBP, and TMZ, alone and in combination, significantly decreased the expression of Bcl-2, p-PI3K, and p-Akt, and increased the expression of Bax. Conclusion: Both LIG and NBP exert anti-glioma effects on their own through the PI3K/Akt pathway and enhance TMZ-mediated anti-glioma efficiency via the same pathway.

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Section: Discussionmentioning

confidence: 99%

“…Emerging evidence indicates that LIG has anti-tumor effects on Ehrlich solid carcinoma (ESC), 29 hepatocellular carcinoma (HCC), 17 prostate cancer, 16 breast cancer 30 and brain tumor, 15 whereas NBP exhibits anti-cancer activity in lung cancer. 19 There are few reports on the therapeutic effects of LIG and NBP, especially NBP, on gliomas.…”

Section: Discussionmentioning

confidence: 99%

Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway

Li,

Zhang,

Liu

et al. 2023

OTT

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“…This pathway can be activated either directly through elevated levels of ROS and VEGF or indirectly through the release of histamine [16]. Autophagy inhibition is a function of mTOR, which enhances the signaling pathways of MAPK and AKT [8]. Inhibiting PI3K and mTOR has shown promising results in combating tumor cells [6].…”

Section: Discussionmentioning

confidence: 99%

“…The control group (no ESC nor echinacoside) did not receive any treatment during the experiment. The ESC group (ESC with no echinacoside) was injected with 200 µL of 2x10 6 tumor cell suspension in phosphate buffer saline into the left hind limb using intramuscular injection [6][7][8]. In the ESC+echinacoside group, the first tumor was injected in rats and left to grow for 14 days, the time taken for the tumor to appear.…”

Section: Animals and Treatment Outlinesmentioning

confidence: 99%

Effects of Echinacoside on Ehrlich Carcinoma in Rats by Targeting Proliferation, Hypoxia and Inflammation

Alshehri,

Albuhayri,

Alanazi

et al. 2023

Cureus

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Background and objectives Ehrlich solid carcinoma (ESC) is a type of tumor originating from a spontaneous mammary adenocarcinoma in mice. It is highly aggressive and fast-growing and can create a solid undifferentiated mass when inserted under the skin. This makes it an ideal model for assessing cancer biology and tumor immunology. Echinacoside is a natural phenylethanoid glycoside with anti-inflammatory, anti-endoplasmic reticulum stress, anti-oxidative stress, and other beneficial properties. This study explored the potential anti-cancer benefits of echinacoside in rats with ESC. The study also analyzed its effects on tumor cell proliferation, differentiation, motility, and inflammation. Methods The study involved injecting rats with tumors in their left hind limb using an intramuscular injection of 2×10 6 cells. After 14 days, some rats were given a daily intraperitoneal dose of 30 mg/kg echinacoside for three weeks. Muscle samples were then analyzed under an electron microscope. In addition, gene expression and protein levels of various factors such as phosphoinositide 3-kinases (PI3K), mammalian target of rapamycin (mTOR), hypoxia-inducible factor (HIF)-1α, cyclin D1, cyclin-dependent kinase 2 (CDK2), tumor necrosis factor (TNF)-α, and nuclear factor (NF)κB were evaluated in another part of the muscle samples. Results After being treated with echinacoside, the ESC rats experienced a significant increase in their mean survival time from 27 days to 48 days. This treatment also resulted in a decrease in the volume and weight of the tumor. Upon examining the tumor tissue under an electron microscope, signs of damage such as pleomorphic cells, necrosis, nuclear fragmentation, membrane damage with cytoplasmic content spilling, and loss of cellular junction were observed. However, the treatment with echinacoside was effective in improving these effects. Furthermore, the expression of PI3K, mTOR, HIF-1α, cyclin D1, CDK2, TNF-α, and NFκB was significantly reduced due to the echinacoside treatment. Conclusions Our research found that echinacoside has antitumor properties that resulted in a substantial decrease in tumor size and weight, leading to an increase in the average survival time of rats and an improvement in muscle structure. Additionally, echinacoside was shown to ameliorate hypoxia by suppressing HIF-1α, reduce inflammation by decreasing NFκB and TNF-α, decrease proliferation by reducing PI3K, and block cyclin D1 and CDK2 to inhibit differentiation.

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“…Rats were subjected to intramuscular injection of 0.15 ml Ehrlich cells (2×10 6 ) in the thigh of the left hind leg [9,10].…”

Section: Esc Groupmentioning

confidence: 99%

Antitumor Activity of Ferulic Acid Against Ehrlich Solid Carcinoma in Rats via Affecting Hypoxia, Oxidative Stress and Cell Proliferation

Alghamdi,

Khalifah,

Alhawati

et al. 2023

Cureus

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BackgroundFerulic acid is a natural compound commonly found in fruits and vegetables like tomatoes, sweet corn, rice bran, and dong quai. It has various beneficial effects on the body, such as anti-inflammatory, anti-apoptotic, hepatoprotective, cardioprotective, and neuroprotective properties. AimsWe conducted a study to investigate the antitumor activity of ferulic acid against Ehrlich solid carcinoma (ESC), specifically by affecting hypoxia-inducible factor (HIF)-1α and its subsequent effects on other factors like nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), cellular Myc (cMyc), cyclin D1, mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). Materials and methodsThe study involved implanting rats with ESC cells and administering 50 mg/kg of ferulic acid orally daily for eight days. Sections of the muscles with ESC were stained with toluidine blue or immunostained with anti-HIF-1α antibodies. The tumor samples were used to evaluate the expression of HIF-1α, Nrf2, HO-1, cMyc, cyclin D1, mTOR, and STAT3. ResultsFerulic acid increased mean survival time, reduced tumor volume and weight, and improved the appearance of the tumor tissue. Furthermore, ferulic acid significantly elevated the expression of Nrf2 and HO-1, while reducing the expression of HIF-1α, Nrf2, HO-1, cMyc, cyclin D1, mTOR, and STAT3. ConclusionsFerulic acid can reduce tumor size and weight while improving the structure of muscle cells, suggesting it may have antineoplastic activity against ESC. Further investigation revealed that ferulic acid downregulates HIF-1α, increasing the expression of antioxidant proteins Nrf2 and HO-1. Additionally, ferulic acid decreases the expression of proliferation markers cMyc and cyclin D1 and downregulates cellular regulators mTOR and STAT3.Categories: Oncology Keywords: signal transducer and activator of transcription 3 (stat3), nuclear factor erythroid 2-related factor 2 (nrf2), mammalian target of rapamycin (mtor), hypoxia-inducible factor (hif)-1α, heme oxygenase-1 (ho-1), ehrlich solid carcinoma (esc), cyclin d1, cellular myc (cmyc)

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Antitumor Activity of Ligustilide Against Ehrlich Solid Carcinoma in Rats via Inhibition of Proliferation and Activation of Autophagy

Cited by 6 publications

References 38 publications

Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway

Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway

Effects of Echinacoside on Ehrlich Carcinoma in Rats by Targeting Proliferation, Hypoxia and Inflammation

Antitumor Activity of Ferulic Acid Against Ehrlich Solid Carcinoma in Rats via Affecting Hypoxia, Oxidative Stress and Cell Proliferation

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